Triomune is a co-formulation of three drugs commonly used in the management of HIV infection. It contains generic versions of the nucleoside reverse transcriptase inhibitors lamivudine (3TC) and d4T (stavudine) and the non-nucleoside RTI, nevirapine (NVP). It is manufactured by Cipla and available in the following strengths:
Triomune 40 with 40mg d4T, 150mg 3TC, and 200mg NVP for adults and teens ≥60 kilos.
Triomune 30 with 30mg d4T, 150mg 3TC, and 200mg NVP for those between 30 and 60 kilos.
Triomune Junior with 12mg d4T, 60mg 3TC, and 100mg NVP for children from 10 to <30 kilos.
Triomune Baby with 6mg d4T, 30mg 3TC, and 50mg NVP for children less than <10 kilos.
NVP requires a two-week induction phase, in which the three drugs are taken separately. Once this phase is successfully completed, daily treatment regimen consists of one tablet taken twice a day. The combination can be dissolved in water for those who have a hard time swalling tablets.
This is the first generic drug licensed by the US FDA for use in children under the age of 12 receiving treatment through the PEPFAR programme.
One concern about the use of generic drugs is their equivalency to branded formulations. A small, open-label, cross-over study in Ugandan adults compared steady-state pharmacokinetic (PK) parameters and tolerability of generic and branded Triomune 40. After one month of stable therapy with the three drugs, patients were randomised to receive the generic or branded drug formulation. PK assessment was done at one month's time and again after a month on the cross-over version.
Althought the PK profile was similar, plasma concentrations for d4T were significantly lower for the generic formulation.1 When a similar cross-over study had been done in Malawian adults, patients had higher NVP exposures compared with Western HIV-infected patients, but lower generic Cmax (maximum concentraton) d4T values.2
One other study done in Cameroon reported similar PK profiles for generic and branded drugs in adults, but that d4T concentrations were significantly lower for the generic formulation.3
Each of these studies concludes that capacity building for PK research needs to be increased so that generic formulations of ARVs can be studied in populations where they are being used.
In a pharmacokinetic study of over 125 children aged from eight months to 18 years of age, children from Lusaka and Blantyre received Triomune tablets that had been halved or quartered. Researchers found that the target NVP dose (>300mg/m2)was not reached in over half of the children, with children weighing less than 30kg significantly more likely to have sub-optimal concentrations. The median NVP concentration was 6mg/l, but 21% of those receiving quarter or half tablets had concentrations below 3mg/l, a sub-therapeutic drug concentration. Thirty-five per cent of children under the age of three had sub-therapeutic drug concentrations, compared to 25% of seven to ten year-olds and 9% of those aged eleven and over.4
Children with wasting had higher NVP concentrations than children of average body weight (reported as body mass index for age), but stunted children had lower than average NVP concentrations.
A Zambian paediatric study in children who were predominantly malnourished indicated that the generic PK drug levels were appropriate for children weighing six kilos or more, but that unequal dosing occurred in d4T and 3TC levels for children weighing less than six kilos.5